KYSA-3: A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Refractory Lupus Nephritis

Kyverna Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Lupus Nephritis - WHO Class IV; Lupus Nephritis; Lupus Nephritis - WHO Class III

Treatments: Biological: KYV-101 anti-CD19 CAR-T cell therapy; Drug: Standard lymphodepletion regimen

Study type: Interventional

Funder types: Industry

Identifiers

NCT06342960

KYSA-3

KYV101-003

Details and patient eligibility

About

A Study of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Subjects With Refractory Lupus Nephritis

Full description

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a wide spectrum of organ involvement and disease severity. Renal involvement (categorized as lupus nephritis [LN]) may occur in approximately 50% of SLE patients and is marked by proteinuria, microscopic hematuria, and varying degrees of renal insufficiency. B cells play a central role in the pathogenesis of SLE and LN, with autoantibodies developing as an early finding, and local, tissue resident B cells producing pathogenic autoantibodies and driving inflammation and tissue damage over time. CD19-targeted chimeric antigen receptor (CAR) T cells harness the ability of cytotoxic T cells to directly and specifically lyse target cells to effectively deplete B cells in the circulation and in lymphoid and potentially non-lymphoid tissues. KYV-101, a fully human anti-CD19 CAR T-cell therapy, will be investigated in adult subjects with refractory lupus nephritis.

Enrollment: 32 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥18 years
2. Clinical diagnosis of SLE according to 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria
3. Biopsy-proven proliferative LN Class III or IV according to 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria
4. Positive anti-nuclear antibody (ANA) (titer ≥1:80 ), anti-dsDNA (≥30 IU/mL on enzyme-linked immunosorbent assay [ELISA]), or anti-Smith at screening or by documented medical history
5. Up to date on recommended vaccinations, including against coronavirus disease 2019/ severe acute respiratory syndrome coronavirus 2 (Covid-19/SARS-Cov-2), per Centers for Disease Control and Prevention (CDC) or institutional guidelines for immune compromised individuals

Exclusion criteria

1. Rapidly progressive glomerulonephritis; history of or currently active severe central nervous system (CNS) lupus, including cerebritis, cerebrovascular accident, and seizures

2. Prior treatment with cellular therapy (CAR-T) or gene therapy product directed at any target

3. History of allogeneic or autologous stem cell transplant

4. Evidence of active hepatitis B or hepatitis C infection

5. Positive serology for HIV

6. Primary immunodeficiency

7. History of splenectomy

8. History of stroke, seizure, dementia, Parkinson's disease, coordination movement disorder, cerebellar diseases, psychosis, paresis, aphasia, and any other neurologic disorder investigator considers would increase the risk for the subject.

9. Impaired cardiac function or clinically significant cardiac disease

10. Previous or concurrent malignancy with the following exceptions:

    1. Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to screening)
    2. In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to screening
    3. A primary malignancy which has been completely resected, or treated, and is in complete remission for at least 5 years prior to screening

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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32 participants in 2 patient groups

KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 1)

Experimental group

Description:

Dosing with KYV-101 CAR T cells

Treatment:

Drug: Standard lymphodepletion regimen

Biological: KYV-101 anti-CD19 CAR-T cell therapy

KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 2)

Experimental group

Description:

Recommended Phase 2 Dose

Treatment:

Drug: Standard lymphodepletion regimen

Biological: KYV-101 anti-CD19 CAR-T cell therapy